This Phase I proposal for development of a plasma-based diagnostic for steatohepatitis will be based on measuring lipid biomarkers in individuals with and without the liver disease. Plasma or serum samples will be collected from normal individuals and patients with advanced steatohepatitis as measured by liver biopsy. The specific aims are to analyze and profile structural changes in plasma and VLDL metabolites that may indicate tissue or metabolic changes, quantify eicosanoids in plasma produced by macrophages in response to inflammation, and correlate the metabolic changes in the liver with plasma biomarkers. This study will be related to the research topic by developing analytical tools to identify biomarkers of steatosis and markers that will be predictive of inflammation and tissue damage that occurs with oxidative stress. Based on plasma metabolite profiles, Phase II research would seek to develop markers to diagnose and differentiate steatosis and steatohepatitis from other liver diseases, correlate these markers with the stage of the disease, and use these markers to monitor the effectiveness of treatment.